Staphylococcus aureus NAD kinase is required for envelop and antibiotic stress responses

Microbes Infect. 2024 May-Jun;26(4):105334. doi: 10.1016/j.micinf.2024.105334. Epub 2024 Mar 30.

Abstract

Global burden of infectious diseases and antimicrobial resistance are major public health issues calling for innovative control measures. Bacterial NAD kinase (NADK) is a crucial enzyme for production of NADP(H) and growth. In Staphylococcus aureus, NADK promotes pathogenesis by supporting production of key virulence determinants. Here, we find that knockdown of NADK by CRISPR interference sensitizes S. aureus to osmotic stress and to stresses induced by antibiotics targeting the envelop as well as replication, transcription and translation. Thus, NADK represents a promising target for the development of inhibitors which could be used in combination with current antibiotics.

Keywords: Antibiotics; NAD kinase; Staphylococcus aureus.

MeSH terms

  • Anti-Bacterial Agents* / pharmacology
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Gene Expression Regulation, Bacterial
  • Gene Knockdown Techniques
  • Humans
  • Osmotic Pressure
  • Phosphotransferases (Alcohol Group Acceptor)* / genetics
  • Phosphotransferases (Alcohol Group Acceptor)* / metabolism
  • Staphylococcus aureus* / drug effects
  • Staphylococcus aureus* / enzymology
  • Staphylococcus aureus* / genetics
  • Stress, Physiological

Substances

  • NAD kinase
  • Anti-Bacterial Agents
  • Phosphotransferases (Alcohol Group Acceptor)
  • Bacterial Proteins